Discovery of a Selective and CNS Penetrant Negative Allosteric Modulator of Metabotropic Glutamate Receptor Subtype 3 with Antidepressant and Anxiolytic Activity in Rodents

Journal of Medicinal Chemistry

Volumn 58, Issue 18, 2015, Pages 7485-7500

  Engers, Julie L ^a   Rodriguez, Alice L ^a   Konkol, Leah C ^a,c   Morrison, Ryan D ^a,d   Thompson, Analisa D ^a   Byers, Frank W ^a   Blobaum, Anna L ^a   Chang, Sichen ^a   Venable, Daryl F ^a,e   Loch, Matthew T ^a   Niswender, Colleen M ^a   Daniels, J Scott ^a,d   Jones, Carrie K ^a   Conn, P Jeffrey ^a   Lindsley, Craig W ^a,b   Emmitte, Kyle A ^a,b,f  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VANDERBILT UNIVERSITY   (United States)

^c Clinical Development   (United States)

^d Sano Informed Prescribing   (United States)

^e Lead Optimization Toxicology and Pharmacology   (United States)

^f UNIVERSITY OF NORTH TEXAS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 [1 [(TERT BUTOXYCARBONYL)AMINO]PROPAN 2 YL] 1H PYRAZOLE 3,5 DICARBOXYLIC ACID; 2 (HYDROXYMETHYL) 5 (4 METHOXYBENZYL) 7 METHYL 6,7 DIHYDROPYRAZOLO[1,5 A]PYRAZIN 4(5H) ONE; 2 [[(5 CHLOROPYRIDIN 2 YL)OXY]METHYL] 5 (2 FLUOROPYRIDIN 3 YL) 7 METHYL 6,7 DIHYDROPYRAZOLO[1,5 A]PYRAZIN 4(5H) ONE; 2 [[(5 CHLOROPYRIDIN 2 YL)OXY]METHYL] 5 (4 METHOXYBENZYL) 7 METHYL 6,7 DIHYDROPYRAZOLO[1,5 A]PYRAZIN 4(5H) ONE; 2 [[(5 CHLOROPYRIDIN 2 YL)OXY]METHYL] 7 METHYL 6,7 DIHYDROPYRAZOLO[1,5 A]PYRAZIN 4(5H) ONE; 5 (4 METHOXYBENZYL) 7 METHYL 4 OXO 4,5,6,7 TETRAHYDROPYRAZOLO[1,5 A]PYRAZINE 2 CARBOXYLIC ACID; 7 METHYL 4 OXO 4,5,6,7 TETRAHYDROPYRAZOLO[1,5 A]PYRAZINE 2 CARBOXYLIC ACID; ANTIDEPRESSANT AGENT; ANXIOLYTIC AGENT; CYTOCHROME P450 1A2; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; KETAMINE; METABOTROPIC RECEPTOR 2; METABOTROPIC RECEPTOR 3; METABOTROPIC RECEPTOR ANTAGONIST; PYRAZINE DERIVATIVE; UNCLASSIFIED DRUG; CALCIUM; FUSED HETEROCYCLIC RINGS; METABOTROPIC RECEPTOR; PYRIDINE DERIVATIVE; VU0650786;

ALLOSTERISM; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIDEPRESSANT ACTIVITY; ARTICLE; CALCIUM MOBILIZATION; CENTRAL NERVOUS SYSTEM; CONTROLLED STUDY; DEPRESSION; DOSE RESPONSE; DRUG CLEARANCE; DRUG EFFICACY; DRUG PENETRATION; DRUG RECEPTOR BINDING; DRUG SCREENING; DRUG SELECTIVITY; DRUG SYNTHESIS; DRUG TISSUE LEVEL; ELIMINATION HALF-LIFE; ENZYME INHIBITION; FORCED SWIM TEST; HEPATIC CLEARANCE; IC50; INTRINSIC CLEARANCE; LIPOPHILICITY; LIVER MICROSOME METABOLISM; MALE; METABOLIC STABILITY; MOUSE; NONHUMAN; RAT; RODENT MODEL; STRUCTURE ACTIVITY RELATION; TISSUE DISTRIBUTION; TRANQUILIZING ACTIVITY; ANIMAL; BRAIN; CHEMISTRY; DOG; HUMAN; LIVER MICROSOME; MDCK CELL LINE; METABOLISM; PERMEABILITY; STEREOISOMERISM;

ALLOSTERIC REGULATION; ANIMALS; ANTI-ANXIETY AGENTS; ANTIDEPRESSIVE AGENTS; BRAIN; CALCIUM; DOGS; HETEROCYCLIC COMPOUNDS, 2-RING; HUMANS; MADIN DARBY CANINE KIDNEY CELLS; MICE; MICROSOMES, LIVER; PERMEABILITY; PYRIDINES; RATS; RECEPTORS, METABOTROPIC GLUTAMATE; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84942279943     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.5b01005     Document Type: Article

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